The biology of child maltreatment

Content provided by the Faculty of the Harvard Medical School

The biology of child maltreatment

How abuse and neglect of children leave their mark on the brain.

Scientists are discovering that early experiences can have profound long-term effects on the biological systems that govern responses to stress. If these systems lack the environment required for normal development, they may fail to function as evolution designed them. Effects on the maturing brain can be subtle as well as obvious. Disturbances at a critical time early in life may exert a disproportionate influence, creating the conditions for childhood and adult depression, anxiety, and post-traumatic stress symptoms.

The body and brain adapt to acute stress — originally, a threat to survival or bodily integrity — through the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The hypothalamus, at the base of the brain, secretes corticotropin-releasing factor (CRF), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal glands and causes the release of the stress hormones cortisol and adrenaline (epinephrine), mobilizing the body and mind for fighting or fleeing. Blood pressure and blood sugar levels rise, breathing and heart rate increase, muscles tense, and we feel anger, anxiety, or fear. The system is controlled by feedback: A high level of stress hormones signals the hypothalamus to stop issuing CRF. Along with the HPA axis, the sympathetic nervous system is activated, as CRF influences circuits that use the neurotransmitters dopamine, norepinephrine, and serotonin.

If the stress response is provoked too often or for too long, it becomes less adaptive. A person under chronic stress, with no hope of relief, is constantly on guard and never able to relax, psychologically or physiologically. The feedback mechanism loses its sensitivity, and the system fails to shut off.

Depression bears some resemblance to an acute stress response that persists when it is no longer needed. The adrenal glands produce more cortisol, and an injection of the synthetic stress hormone dexamethasone often does not have the normal feedback effect of suppressing the release of cortisol. Depressed persons may have excess CRF in the spinal fluid and greater expression (activation) of genes for producing CRF receptors in the brain, especially the centers of memory and strong emotions in the hippocampus and amygdala. Instead of being temporarily and appropriately alert and vigilant, a depressed person is likely to be either chronically lethargic and apathetic or agitated, anxious, and sleepless.

It has long been known that childhood abuse and neglect and the loss of a parent are associated with adult psychiatric disorders, including depression, anxiety, and post-traumatic symptoms. Apart from heredity and recent stress, child maltreatment is the most common predictor of major depression in adults. Now researchers are discovering how early experiences affect the ability to maintain psychological and physical balance. Childhood trauma and loss can cause prolonged hypersensitivity to stress by upsetting the regulation of the HPA axis and sympathetic nervous system.

Receptors in the brain are sensitive to CRF in infancy and even before birth. A depressed mother raises the level of CRF in the child she is carrying. Six-month-old children of women who were depressed or abused while pregnant secrete cortisol at a higher than average level in response to mild stress.

Some of these effects can be demonstrated experimentally in laboratory animals. Rat pups were removed from their mothers repeatedly before weaning. The mothers tended to neglect pups treated this way, giving them little attention and feeding them last. When tested as adults, the rats overreacted to mild stress and were more likely to suffer from a rat equivalent of depression — passivity in difficult situations and a weak response to rewards like sugar water. Young hamsters placed in a cage with mature hamsters that threaten and attack them show lasting changes in the brain circuitry using serotonin and other neurotransmitters that regulate mood and aggression.

People who suffer childhood maltreatment are more vulnerable to post-traumatic stress symptoms after further traumatic childhood or adult experiences because their bodies and brains have “learned” that they cannot count on protection and solace in distressing situations. The symptoms of post-traumatic stress disorder (PTSD) include heightened anxiety and jumpiness, intrusive memories and flashbacks, avoidance of situations, places, and people reminiscent of the traumatic event, and often emotional numbness, loss of trust in others, and an aversion to intimate relationships.

PTSD is usually preceded by an acute stress reaction that involves activity of the HPA axis and sympathetic nervous system. The amygdala, the brain’s center for registering fear, intensifies memories of trauma through its links to the hypothalamus, hippocampus, and cerebral cortex. The aroused amygdala strengthens connections that produce emotionally charged memories. Its function is to make these memories difficult to eradicate so that we will recognize the threat if it reappears. In this way, traumatic experiences are preserved in long-term memory, and anything even remotely reminiscent of the trauma may serve as a cue to revive the experience. Re-experiencing further strengthens the emotional associations, which in turn further consolidates the memory in a vicious cycle.

Excess cortisol production can damage the hippocampus, disrupting the connections between neurons and eventually cause the neurons themselves to degenerate. Brain-derived neurotrophic factor (BDNF), which helps the hippocampus to generate neurons, is reduced in rats who have been separated from their mothers. One study found a shrunken hippocampus in depressed women who were traumatized as children. In another study, women with post-traumatic stress disorder resulting from child abuse showed abnormal activity in the frontal lobes.

Researchers are looking for ways to prevent and reverse the harm, either in childhood or later in life. Rat pups from a genetically anxious strain respond much better to stress as adults if they are adopted by unusually attentive foster mothers who constantly lick and groom them. In a strain of rats sensitive to alcohol, the risk of addiction is increased by early separation from their mothers. Selective serotonin reuptake inhibitors (Prozac and company) may partially reverse the effect. These drugs may also promote the regeneration of neurons in the hippocampus.

Drugs that interfere with the activity of CRF are being considered for the treatment of depression. Mifepristone (RU-486), best known as an abortion drug, is a CRF antagonist that has shown some promise as a treatment for psychotic depression. Propranolol (Inderal), a drug that blocks nerve receptors for norepinephrine in the amygdala, apparently reduces arousal in response to memories of a traumatic experience when it is taken for several weeks starting immediately after the trauma. It could be warding off PTSD by preventing traumatic memories from working their way indelibly into the brain.

Psychological treatment for post-traumatic stress disorder also involves retraining the amygdala to respond differently when traumatic memories recur. And it may turn out that sometimes the nature of the childhood experience determines the choice of treatment. In one study, an antidepressant was compared to cognitive behavioral therapy and a combination of the two in the treatment of severely depressed women. The combination was best for the group as a whole, but for those who had suffered traumatic experiences in childhood, the drug was less effective than psychotherapy and the combination was no better than psychotherapy alone.

Maltreatment does not, of course, cause the same changes in neurotransmitter or stress hormone activity or long-term brain function in everyone. Individual genetic characteristics are important; for example, there is evidence that one variant of a gene that governs the reabsorption of serotonin promotes greater activity in the amygdala and makes children more vulnerable to stress. The kind of stress — parental loss; neglect; physical, sexual, or emotional abuse — may also make a difference. And some maltreated children, instead of developing adult psychiatric disorders, come through relatively unscathed.

Learning more about the biological consequences of child maltreatment through brain imaging and molecular genetic studies will help in defining more precisely the causes and nature of depression, anxiety, and post-traumatic stress symptoms. Just as important, it may improve our understanding of how resilient children maintain hope, control anxiety, and achieve normal development despite abuse and neglect.

Last updated:	August 21, 2006